Impact of availability of direct-acting antivirals for hepatitis C on Canadian hospitalization rates, 2012-2016.

BACKGROUNDS: Hospitalizations associated with hepatitis C virus (HCV) infection and liver disease increased on average by 6.0% per year from 2004 to 2010 in Canada and were projected (in 2010) to increase by another 4% by 2016. The first generation of direct-acting antivirals (DAAs) became available in 2012. In 2014, a second generation of effective and well-tolerated DAA therapy was authorized in Canada. The impact of DAA therapy on the HCV-associated disease burden in Canada has not been documented. OBJECTIVES: To assess the potential impact of DAA therapy on the disease burden by a) comparing the actual hospitalization rates associated with HCV infection and liver disease following the introduction of DAAs in Canada with the 2010 baseline projection and b) documenting the associated uptake of anti-HCV therapy. METHODS: The hospital records of inpatients diagnosed with chronic HCV and chronic liver disease were extracted from the Canadian Discharge Abstract Database (DAD) by fiscal year for 2004-2016. We compared the actual number of hospitalizations to the baseline projection by year and for selected 5-year birth cohorts (1925-1989). The monthly number of new prescriptions for anti-HCV regimens was extracted from the IQVIA CDH CompuScript database (formerly IMS Health), aggregated to annual levels by age group and compared with hospitalization trends. RESULTS: Compared to the baseline projection, there was a slight reduction in hospitalizations in 2014/15 and 2015/16. This slight reduction was followed by a more significant decline in 2016/17 (32% below expected; 95% confidence interval [CI]: 27%-37%). The largest declines were observed for patients born before 1960 (age 55 or older) at 40% below expected in 2016/17. The number of new anti-HCV prescriptions increased from 5,484 in fiscal year 2012/13 to a peak of 17,775 in 2015/2016. The number of new prescriptions corresponds to approximately 1.3 and five times the number of hospitalizations in 2012/13 and 2015/16, respectively. CONCLUSIONS: In Canada there has been a modest decrease in HCV and liver-related hospitalizations following a significant increase in uptake of second-generation DAAs in 2015. However, the burden is still high. Linked health administrative databases created to monitor the disease burden in the new treatment era should provide additional insight with the linkage of treatment history and disease stage to individual outcomes.

What are Canadian primary care physicians prescribing for the treatment of gonorrhea?

BACKGROUND: Cases of Neisseria gonorrhea are on the rise in Canada, which-if undetected or undertreated-can lead to morbidity and infertility. In addition, the number of antimicrobial resistant strains is also increasing creating the risk that N. gonorrhea may become untreatable. In 2013, the Public Health Agency of Canada (PHAC) released Canadian recommendations for the management and treatment of gonorrhea that identified the need for combination therapy to address and minimize antimicrobial resistance. However, the level of awareness and uptake of these guidelines is not well-known. OBJECTIVES: To assess primary care physicians' prescribing practices for the management and treatment of gonorrhea. METHODS: After validity testing, two online cross-sectional surveys were conducted with a convenience sample of Canadian physicians. Physicians answered true/false statements and open-ended questions relating to three clinical scenarios: 1) suspected anogenital infection drawing from a population of men who have sex with men (MSM); 2) suspected anogenital infection drawing from a non-MSM population; and, 3) suspected pharyngeal infection drawing from any population. Frequencies of responses were calculated for the statements. Open-ended responses were recoded into treatment categories and frequencies were calculated for each scenario. RESULTS: A total of 625 physicians completed the survey. Most physicians (60%-95%) accurately identified knowledge statements regarding pharmaceutical management, partner notification and public health reporting. For all clinical scenarios, 30%-35% of physicians did not provide any treatment information, approximately 30% indicated treating with cephalosporin monotherapy, 20%-25% indicated they would prescribe a cephalosporin and azithromycin and a minority of physicians identified other treatment options. When physicians were asked about the purpose of the second antibiotic, azithromycin, 49% indicated it was to provide presumptive treatment for gonorrhea and chlamydia. Forty-one percent indicated it was to provide presumptive treatment for chlamydia only. CONCLUSION: This convenience sample suggests that although knowledge of pharmaceutical management, partner notification, and public health reporting is high, the use of combination therapy to deter the development of antimicrobial resistant gonorrhea may not be widespread among primary care physicians. In light of both the growing incidence of N. gonorrhea and the rising rates of antimicrobial resistance in Canada, consideration on how to improve awareness and update of best prescribing practices in primary care may be indicated.

Benzathine penicillin G for the management of early syphilis among HIV co-infected persons: A systematic review.

BACKGROUND: The optimal treatment for syphilis in people who are human immunodeficiency virus (HIV) positive is controversial. OBJECTIVE: To assess the efficacy of three doses versus a single dose of long acting Benzathine Penicillin G (BP-G) for the effective management of early syphilis among HIV co-infected populations. METHODS: A systematic search of the published literature was conducted using MEDLINE and EMBASE databases to identify clinical and observational studies published between January 2010 and May 2015. Inclusion criteria were: publication in English or French, populations co-infected with HIV and early syphilis, treatment with BP-G and outcomes related to syphilis treatment. All articles underwent a risk of bias assessment and data extraction was completed on all included studies. RESULTS: Seven studies were eligible for final inclusion, data extraction and analysis. The evidence from the final included studies were from non-randomized controlled trials. In general, no significant differences were found between groups treated with one versus two or more doses of BP-G; but there was a trend toward longer time to treatment failure with three doses. Differences in methodology limit the ability to draw any firm conclusions on the relative efficacy between these two treatment regimens. CONCLUSION: Insufficient data exist to ascertain whether or not there is an added benefit from additional doses of BP-G for the treatment of early syphilis with HIV co-infection. A high-quality, randomized controlled trial is needed to definitively nswer this question.

Does suppressive antiviral therapy for herpes simplex virus prevent transmission in an HIV-positive population? A systematic review.

BACKGROUND: Among individuals with genital herpes simplex virus (HSV), co-infection with human immunodeficiency virus (HIV) has been shown to increase the frequency and severity of HSV symptoms, HSV shedding, and risk of HSV transmission. OBJECTIVE: To assess whether suppressive antivirual therapy for genital HSV in an HIV-positive populatation prevents HSV transmission to a susceptible partner. METHODS: A systematic search of the literature was conducted using MEDLINE and EMBASE databases to identify randomized controlled trials published between January 2005 and June 2015. Inclusion criteria were trials written in English or French utilizing suppressive antiviral therapies for HSV. Studies had to report on outcomes related to HSV transmission from HIV-positive populations. Surrogate markers of HSV transmission risk, such as HSV detection and viral load, were also included. Articles underwent a risk of bias assessment, and those with low risk of bias underwent data extraction to complete a narrative synthesis. RESULTS: This review identified thirteen papers. Only one study directly measured transmission of HSV. The overall transmission rate was <10%, and suppressive antiviral therapy had no significant protective effect (9% transmission rate in the acyclovir group vs. 6% in the placebo group; hazard ratio [HR]: 1.35, 95% CI: 0.83-2.20). The remaining 12 papers addressed surrogate markers of transmission risk: HSV detection and viral load. Suppressive acyclovir appears to be effective in reducing HSV detection among HIV-positive populations, but it does not appear to reduce viral load. Suppressive valacyclovir may be effective in reducing HSV detection and viral load among HIV-positive patients who are antiretroviral therapy (ART)-naïve, but its effect appears to be nullified among those concurrently on ART. CONCLUSION: Based on current evidence, suppressive antiviral therapy may reduce HSV detection and viral load, but its impact on HSV transmission is unclear. Clinicians should caution HIV-positive patients with HSV that suppressive therapy may not reduce risk of HSV transmission to susceptible partners.

Hepatitis C in Canada and the importance of risk-based screening.

Chronic hepatitis C (CHC) remains a public health issue affecting an estimated 220,000 individuals in Canada. In 2011, approximately 44% of those with CHC were unaware of their infection. Hepatitis C is infectious in origin, and if left untreated, can lead to significant morbidity and mortality in its chronic form, including liver cirrhosis, hepatocellular carcinoma and liver failure. These health outcomes are associated with comorbidities, adding a burden to the Canadian health care system. Recent advancements in the treatment of hepatitis C have changed the clinical landscape. In Canada, the prevalence of incident cases is higher in specific population groups. Injection drug use (IDU) currently accounts for the highest proportion of new hepatitis C virus (HCV) infection. It is unclear to what extent HCV infection through health care or personal services use contributed to current prevalent cases of CHC. The Canadian Task Force on Preventive Health Care (CTFPHC) is currently reviewing the evidence for different approaches to HCV screening and the benefits and harms of screening. Risk-based screening remains critical to detecting hepatitis C as knowing one's status has been linked to the cascade of care and improved population health outcomes. This article intends to highlight risk factors associated with the acquisition of HCV so that health care providers can screen, where appropriate, and detect CHC.

Prevalence of self-reported hysterectomy among Canadian women, 2000/2001-2008.

BACKGROUND: Hysterectomy is one of the most frequently performed surgical procedures among Canadian women. The consequence is a population that no longer requires cervical cancer screening. The objective of our analysis was to provide more accurate estimates of eligible participation in cervical screening by estimating the age-specific prevalence of hysterectomy among Canadian women aged 20 to 69 by province and territory between 2000/2001 and 2008. METHODS: Self-reported hysterectomy prevalence was obtained from the 2000/2001, 2003 and 2008 Canadian Community Health Survey. Age-specific prevalence and 95% confidence intervals (CIs) were estimated for Canada and provinces and territories for the three time periods. RESULTS: Interprovincial variations in hysterectomy prevalence were observed among women in each age group and time period. Among women aged 50 to 59, prevalence was as high as 35.1% (95% CI: 25.8-44.3) (p<.01) in 2008 and appeared to decrease in all provinces from 2000/2001 to 2008. CONCLUSION: Interprovincial and time period variation suggest that using hysterectomy prevalence to adjust the population eligible for cervical cancer screening may be helpful to inform more comparable screening participation rates. In addition, both cervical cancer incidence and mortality rates can be adjusted by hysterectomy to ensure estimates across time and provinces and territories are also comparable.

TITRE: Prévalence de l'hystérectomie autodéclarée chez les Canadiennes, 2000-2001 à 2008. INTRODUCTION: L'hystérectomie est l'une des interventions chirurgicales les plus souvent pratiquées chez les Canadiennes. Le dépistage du cancer du col de l'utérus n'est donc plus nécessaire dans cette population. Notre analyse visait à obtenir des estimations plus exactes de la participation au dépistage du cancer du col utérin dans la population admissible en déterminant la prévalence de l'hystérectomie selon l'âge chez les Canadiennes de 20 à 69 ans, par province ou territoire, entre 2000-2001 et 2008. MÉTHODOLOGIE: Les données relatives à la prévalence de l'hystérectomie autodéclarée ont été tirées de l'Enquête sur la santé dans les collectivités canadiennes de 2000-2001, de 2003 et de 2008. Nous avons estimé la prévalence selon l'âge et les intervalles de confiance (IC) à 95 % pour le Canada et les provinces et territoires pour les trois périodes. RÉSULTATS: Des variations interprovinciales de la prévalence de l'hystérectomie ont été observées chez les femmes dans chaque groupe d'âge et au cours de chaque période. Chez les femmes de 50 à 59 ans, la prévalence a semblé diminuer dans toutes les provinces entre 2000-2001 et 2008, le plus haut taux provincial atteint en 2008 étant 35,1% (IC à 95%: 25,8 à 44,3; p < 0,01). CONCLUSION: Les variations selon les provinces et au cours du temps laissent penser qu'il pourrait être bon d'utiliser la prévalence de l'hystérectomie pour ajuster la population admissible au dépistage du cancer du col de l'utérus, de manière à obtenir des taux plus comparables de participation. Il est en outre possible d'ajuster à la fois les taux d'incidence du cancer du col utérin et de mortalité par cancer du col utérin de façon à ce que les estimations dans le temps et pour l'ensemble des provinces et territoires soient comparables.

A review of screening mammography participation and utilization in Canada.

INTRODUCTION: Participation rate is an important indicator for a screening program's effectiveness; however, the current approach to measuring participation rate in Canada is not comparable with other countries. The objective of this study is to review the measurement of screening mammography participation in Canada, make international comparisons, and propose alternative methods. METHODS: Canadian breast cancer screening program data for women aged 50 to 69 years screened between 2004 and 2006 were extracted from the Canadian Breast Cancer Screening Database (CBCSD). The fee-for-services (FSS) mammography data (opportunistic screening mammography) were obtained from the provincial ministries of health. Both screening mammography program participation and utilization were examined over 24 and 30 months. RESULTS: Canada's screening participation rate increases from 39.4% for a 24-month cut-off to 43.6% for a 30-month cut-off. The 24-month mammography utilization rate is 63.1% in Canada, and the 30-month utilization rate is 70.4%. CONCLUSION: Due to the differences in health service delivery among Canadian provinces, both programmatic participation and overall utilization of mammography at 24 months and 30 months should be monitored.

Structure and giant magnetoresistance behaviour of Co-Cu/Cu multilayers electrodeposited under various deposition conditions.

Electrodeposited Co-Cu/Cu multilayers were prepared under a variety of deposition conditions on either a polycrystalline Ti foil or on a silicon wafer covered by a Ta buffer and a Cu seed layer. X-ray diffraction (XRD) revealed a strong (111) texture for all multilayers with clear satellite peaks for the multilayers on Si/Ta/Cu substrates, in some cases for up to three reflections. Cross-sectional transmission electron microscopy investigations indicated a much more uniform multilayer structure on the Si/Ta/Cu substrates. The bilayer periods from XRD satellite reflections were in reasonable agreement with nominal values. An analysis of the overall chemical composition of the multilayers gave estimates of the sublayer thickness changes due to the Co-dissolution process during the Cu deposition pulse. The XRD lattice spacing data indicated a behaviour close to a simple "multilayer" Vegard's law which was, however, further refined by taking into account elastic strains as well. In agreement with the structural studies, magnetoresistance data also indicated the formation of more perfect multilayers on the smooth Si/Ta/Cu substrates. An analysis of the magnetoresistance behaviour revealed the presence of superparamagnetic (SPM) regions in the magnetic layers. The contribution of these SPM regions to the total observed giant magnetoresistance was found to be dominating under certain deposition conditions, e.g., for magnetic layer thicknesses less than 1 nm (about 5 monolayers).